Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats

Megan M. Kangiser, Linda P. Dwoskin, Guangrong Zheng, Peter A. Crooks, Dustin Stairs

Research output: Contribution to journalArticle

Abstract

Methamphetamine is a potent psychostimulant with high abuse rates. Currently, there is no Food and Drug Administration-approved pharmacotherapy for methamphetamine addiction. Ideally, a pharmacotherapy should selectively decrease methamphetamine self-administration without affecting responding for other reinforcers. One way to test this is with the use of a multiple schedule of reinforcement, in which drug and food are available in alternating components within a session. The present study evaluated GZ-793A, a vesicular monoamine transporter-2 inhibitor, and varenicline, a partial agonist at α4β2 and full agonist at α7 nicotinic acetylcholine receptors, for their ability to decrease methamphetamine and food self-administration using a multiple schedule of reinforcement. Male Sprague-Dawley rats self-administered methamphetamine (0.03 mg/kg/intravenous infusion) and food pellets under a multiple schedule of reinforcement. GZ-793A or varenicline was administered before multiple schedule sessions. GZ-793A (5 and 20 mg/kg) significantly decreased methamphetamine intake compared with saline and did not alter food-maintained responding. In contrast, varenicline decreased methamphetamine intake less specifically across time. The results suggest that vesicular monoamine transporter-2 inhibition may be a viable pharmacological target for the treatment of methamphetamine-use disorders.

Original languageEnglish (US)
Pages (from-to)87-97
Number of pages11
JournalBehavioural Pharmacology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2018

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Reinforcement Schedule
Self Administration
Methamphetamine
Vesicular Monoamine Transport Proteins
Food
Drug Therapy
Aptitude
N-(1,2-dihydroxylpropyl)-2,6-di-(4-methoxyphenethyl)piperidine
Varenicline
Nicotinic Receptors
United States Food and Drug Administration
Intravenous Infusions
Sprague Dawley Rats
Appointments and Schedules
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats. / Kangiser, Megan M.; Dwoskin, Linda P.; Zheng, Guangrong; Crooks, Peter A.; Stairs, Dustin.

In: Behavioural Pharmacology, Vol. 29, No. 1, 01.01.2018, p. 87-97.

Research output: Contribution to journalArticle

Kangiser, Megan M. ; Dwoskin, Linda P. ; Zheng, Guangrong ; Crooks, Peter A. ; Stairs, Dustin. / Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats. In: Behavioural Pharmacology. 2018 ; Vol. 29, No. 1. pp. 87-97.
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